LY2940680 can inhibit Hh signaling in uman medulloblastoma tumor cell lines and mouse mesenchymal cell lines.LY2940680 treatment induced Caspase-3 activity and reduced proliferation. LY2940680 binds to and inhibits the functional activity of resistant Smo mutant (D473H) produced by treatment with GDC-0449.
In vivo
LY2940680 inhibited Hh regulated gene expression in the subcutaneous xenograft tumor stroma and produced significant anti-tumor activity. In Ptch+/ÿ p53ÿ/ÿ transgenic mice, oral administration of LY2940680 shows remarkable efficacy and significantly improve their survival.